[Advances in immunotherapy for pulmonary sarcomatoid carcinoma].

Pulmonary sarcomatoid carcinoma (PSC) is a rare, poorly differentiated non-small cell lung cancer (NSCLC) that contains sarcomatoid components or sarcomatoid differentiation, and accounts for less than 1% of all lung tumors. Compared to other types of NSCLC, PSC has more invasive biological behavior, is prone to metastasis, and has a higher recurrence rate after early surgery. Its greater resistance to traditional treatments leads to a poorer prognosis compared to other NSCLCs. Immunotherapy offers the possibility of long-term survival for PSC patients.

[Clinical analysis of lung adenocarcinoma with epidermal growth factor receptor mutation transformed into sarcoma].

Objective: To analyze the clinical data of a case of lung adenocarcinoma with Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) resistance transforming into sarcoma, and to conduct a literature review to improve the understanding of the resistance mechanism. Histological transformation is a unique form of acquired resistance of EGFR-TKIs in non-small cell lung cancer (NSCLC). Thereinto, the transformation of small cell carcinoma is more common, and the transformation of sarcoma is rarely reported. Methods: Clinicopathological data on the treatment process, pathological features, and clinical outcome of the patient with EGFR-TKIs-resistance lung adenocarcinoma transforming into sarcoma were collected. The literature was reviewed to analyze the pathogenetic mechanism for sarcomatoid carcinoma or sarcoma transformation after drug resistance of adenocarcinoma, as well as the clinical characteristics of the patients and the corresponding therapeutic schemes. Results: We reported a patient with lung adenocarcinoma who developed EGFR-T790M mutation after first-line treatment with icotinib and sarcoma transformation after second-line treatment with almonertinib. Chemotherapy, radioactive particle implantation, antiangiogenic therapy and immunotherapy were followed, but the results were unsatisfactory. There was no report of EGFR-TKIs-resistant lung adenocarcinoma transforming into sarcoma. Among the 14 reports of adenocarcinoma transforming into sarcomatoid carcinoma, 8 cases had EGFR mutation, 3 cases had ALK mutation, 2 cases had ROS1 mutation, and 1 case had no asscoiated sensitive mutation. The median survival of 14 patients with adenocarcinoma transforming to sarcomatoid carcinoma was only 3 months. Conclusions: Sarcoma transformation can be one of the forms of drug resistance in patients with lung adenocarcinoma with EGFR-TKIs. The prognosis of patients with adenocarcinoma after transformation into sarcoma is poor.

[Treatment of oligoprogression to immunotherapy resistance in advanced non-small cell lung cancer].

In recent years, the incidence of lung cancer has been increasing year by year. Traditional treatments have limited clinical effects in advanced, driver-gene-negative non-small cell lung cancer. Immune checkpoint inhibitors (ICI) have dramatically changed the treatment landscape of advanced non-small cell lung cancer. However, most patients are suffered from primary and acquired resistance inevitably. Oligoprogression is one of the main progression patterns of acquired resistance. Therefore, it is essential to further understand treatment of oligoprogression to immunotherapy resistance. This article aimed to conduct a systematic review of the treatment of oligoprogression to immunotherapy resistance.

[Clinical characteristics of epidermal growth factor receptor-mutated advanced adenocarcinoma transformed into small-cell lung cancer].

Objective: To explore the clinicopathological characteristics and genomic characteristics of four patients with epidermal growth factor receptor(EGFR)-mutated advanced adenocarcinoma transformed into small-cell lung cancer. Methods: Four cases of EGFR-mutated advanced adenocarcinoma of the lung transformed into small-cell lung cancer were studied by clinical data, pathological morphology, immunohistochemistry and gene detection. Result: EGFR-mutated adenocarcinoma of the lung was heterogeneous in clinical and genomic profiles, of ten characterized by RB1, TP53 and PIK3CA mutations. Its transformation into small-cell lung cancer was a particularly aggressive mechanism of drug resistance, but the machanisms were not clear NSE and other tumor indicators had low diagnostic value for transformation. Conclusions: EGFR-mutated adenocarcinoma of the lung transformed into small-cell lung cancer was one of the reasons for EGFR resistance with avery poor prognosis.

[Advances in the study of occult malignant tumor-related pyogenic liver abscesses in the digestive system].

Pyogenic liver abscess (PLA) accompanied by occult malignant tumors is a rare kind of life-threatening disease. Studies have shown that it can predict the occurrence of cancer, especially hepatobiliary and colorectal cancer. The risk of combined occult primary liver cancer, cholangiocarcinoma, and gastrointestinal cancer is high in PLA patients. Malignant tumor-related PLA lacks specific symptoms and signs. The iodine concentration ratio between the energy spectrum CT lesions and normal liver tissue is of certain value in the differentiation of liver cancer and liver abscess. Computed tomography colonography has a dual role. It can screen patients with PLA for occult colorectal cancer and determine the treatment response of abscess lesions. Klebsiella pneumoniae and Escherichia coli is the main microorganism of PLA related to colorectal cancer, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma. PLA treatment related to hepatobiliary malignant tumor has high complications and mortality, and poor prognosis. Most occult colorectal cancers are in the early stage, and their early detection and prognosis are better than those of PLA patients combined with hepatobiliary malignancies.

Mechanism of action of KIAA1456 gene on the proliferation and apoptosis of alveolar epithelial cells.

OBJECTIVE: To explore the mechanism by which KIAA1456 acts on alveolar epithelial cells through lentiviral transfection. MATERIALS AND METHODS: After constructing a KIAA1456 gene vector, 293T cells were co-transfected with lentiviral vectors and after incubation cells were examined by fluorescence microscopy. CCL-149 cells were transfected with LV-KIAA1456 and were examined by fluorescence microscopy. The proliferation capacity of transfected CCL-149 cells was evaluated using flow cytometry. The effect of KIAA1456 overexpression on CCL-149 cells proliferation was studied using the CCK-8 method. RESULTS: The expression level of KIAA1456 in the LV- KIAA1456 group was significantly higher compared with the LV-Con group and the blank group. Compared with the LV-Con and the blank groups, the proportion of responding cells in G2/M phase showed statistically significant differences. Viable cells had adarker color and higher OD value measured by ELISA. Compared with the control and the blank groups, the growth and proliferation in the CCL-149 transfection group were significantly slower. CONCLUSIONS: KIAA1456 gene inhibited the proliferation of CCL-149 cells by negative regulation of the G2/M cell cycle. We suggest that it can be used as a specific target for the treatment of alveolar epithelium.

Inhibition of the integrin/FAK signaling axis and c-Myc synergistically disrupts ovarian cancer malignancy.

Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor. From this screening, JQ1, a potent inhibitor of Myc oncogenic network, emerged as the most robust collaborator. Treatment with a combination of VS-6063 and JQ1 synergistically caused an arrest of tumor cells at the G2/M phase and a decrease in the XIAP-linked cell survival. Our subsequent mechanistic analyses indicate that this functional cooperation was strongly associated with the concomitant disruption of activation or expression of FAK and c-Myc as well as their downstream signaling through the PI3K/Akt pathway. In line with these observations, we detected a strong co-amplification or upregulation at genomic or protein level for FAK and c-Myc in a large portion of primary tumors in the TCGA or a local HGSOC patient cohort. Taken together, our results suggest that the integrin-FAK signaling axis and c-Myc synergistically drive cell proliferation, survival and oncogenic potential in HGSOC. As such, our study provides key genetic, functional and signaling bases for the small-molecule-based co-targeting of these two distinct oncogenic drivers as a new line of targeted therapy against human ovarian cancer.

[Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration in stage â and stage â ¡ of sarcoidosis].

OBJECTIVE: To evaluate the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in stage Ⅰ and stage Ⅱ of sarcoidosis. METHODS: There were 55 patients of sarcoidosis selected from January 2012 to October 2014 in the First Affiliated Hospital of Soochow University. The diagnostic positive rate and the positive rate in stage Ⅰ and Ⅱ patients with sarcoidosis through EBUS-TBNA, conventional transbronchial needle aspiration (cTBNA), endobronchial biopsy (EBB) combined with transbronchial lung biopsy (TBLB) were calculated. The positive rate of single lymph node puncture and the positive rate of different size of lymph node were compared. The difference of the positive rate of lymph nodes in different stations was checked. By calculating the diagnostic yield of EBUS-TBNA in sarcoidosis patients, the practicality and safety of EBUS-TBNA in diagnosing stage Ⅰ or stage Ⅱ sarcoidosis was assessed. RESULTS: Among 55 patients, 46 patients obtained positive results through EBUS-TBNA or cTBNA. There were 18 patients who had only received EBUS-TBNA among a total of 55 patients diagnosed with sarcoidosis, positive results appeared in 17 cases, while cTBNA was 9/15. There were 20 cases diagnosed in which both had EBUS-TBNA and cTBNA. The diagnostic rate of cTBNA combined with EBB and TBLB was 25/26, while combined with EBUS-TBNA was 21/21. Totally 90 lymph nodes were punctured by EBUS-TBNA, in which 65 lymph nodes got the positive results (65/90) while 49 lymph nodes got the positive results by TBNA in 93 punctured lymph nodes (49/93). The diagnostic positive rate in the lymph nodes with a short diameter ≥2 cm was 33/37 by EBUS-TBNA, while it was 12/19 in those whose short diameter 1-<2 cm. By cTBNA, the diagnostic positive rate was 15/26 and 11/28. No serious adverse events occurred. CONCLUSIONS: The diagnosis of sarcoidosis in stage Ⅰ and stage Ⅱ by EBUS-TBNA is safe and effective, while choosing the most noticeable swelling lymph node to puncture is recommended. Combining the EBUS-TBNA with traditional bronchoscope technology can obtain a further higher diagnostic efficiency.

[The clinical characteristics analysis of Escherichia coli bloodstream infection].

OBJECTIVE: To explore the clinical features of Escherichia coli bloodstream infection. METHODS: The clinical data of underlying diseases, antimicrobial susceptibility, temperature at blood sampling, results of routine blood tests, venous catheterization, therapy and prognosis of Escherichia coli bloodstream infection in the First Affiliated Hospital of Soochow University from January 2007 to December 2014 were analyzed retrospectively. The pathogens were routinely isolated and identified. Susceptibilities against antimicrobial agents were determined by Kirby-Bauer methods. RESULTS: All patients had at least one underlying disease. Most of the basic diseases were hematological malignancies, malignant solid tumors, pneumonia and so on. Body temperature was normal in 40 patients (6.4%), fever in 587 patients (93.5%) and low temperature in 1 patient. There were 252 patients with leukopenia (40.1%), 237 patients with granulocytopenia (37.7%) and 216 patients with agranulocytosis. The resistance rate to imipenem was 3.3%, which was the lowest among the total antimicrobial susceptibilities of 628 Escherichia Coli. The extended-spectrum-ß-lactamase (ESBL)-producing strains accounted for 53.8% among the total patients. The resistance rates of ESBLs-producing-Escherichia coli for the Sulfamethoxazole, Ampicillin, Gentamicin, Cefazolin, Cefuroxime, Cefotaxime, Ceftriaxone, Cefepime, Ceftazidime, Cefoperazone, Piperacillin and Ciprofloxacin were 80.2%, 100.0%, 62.4%, 99.1%, 99.1%, 98.8%, 98.2%, 48.5%, 50.6%, 95.0%, 98.2%, 79.6%, respectively, which were higher than that of non-ESBLs-producing-Escherichia coli (67.9%, 79.7%, 47.6%, 50.0%, 47.2%, 41.0%, 40.3%, 27.2%, 24.1%, 40.0%, 56.2%, 58.3%, respectively), the differences were significant statistically (χ(2)=12.33, 75.90, 13.92, 209.00, 224.94, 259.25, 256.59, 27.79, 46.19, 222.85, 165.08, 33.59, all P<0.05). One hundred and seventy eight patients received venous catheterization when blood culture were performed. All the patients received antimicrobial treatment, mainly including carbapenem antibiotics and beta-lactamase inhibitors combinations. Of which 533 patients were improved, the improvement rate was 84.9%. CONCLUSIONS: There are many risk factors in relation to Escherichia coli bloodstream infection. The antimicrobial resistance rate of ESBLs-producing-Escherichia coli is higher than that of none-ESBLs-producing-Escherichia coli. Individualized strategies should be based on antimicrobial sensitivity.

The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cells.

BACKGROUND: Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti-inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase-2 (COX-2) negative colorectal cancer cell lines. MATERIALS AND METHODS: After treatment with various concentrations of ASA, cell proliferation was measured in the human colon cancer cell line SW480. Apoptotic cells were identified by transmission electron microscopy, acridine orange staining, and flow cytometry. The invasive potential of SW480 cells was detected using an in vitro invasion assay. The production of carcinoembryonic antigen was measured by microparticle enzyme immunoassay. Expression of Bcl2, Bax, CD44v6, and nm23 were evaluated by immunocytochemistry. RESULTS: ASA significantly inhibited the proliferation of SW480 cells and stimulated apoptosis. Production of carcinoembryonic antigen and the invasive potential of SW480 cells were also inhibited by ASA. After treatment with ASA, down-regulation of Bcl2 and CD44v6 expression and up-regulation of nm23 expression were observed in SW480 cells. No obvious effect of ASA was found on Bax expression. CONCLUSION: Our findings reveal that ASA inhibits the proliferation and promotes apoptosis in the human colon cancer cell line SW480. Down-regulation of Bcl2 expression might represent a potential mechanism by which ASA induces apoptosis in this COX-2 negative colon cancer cell line. Our results also suggest that ASA decreases the invasive potential of these colon cancer cells. Decreased CEA content and CD44v6 expression and elevated nm23 expression may contribute to the effect of ASA on invasive potential of SW480 colon cancer cells.

Avian reovirus sigma C protein contains a putative fusion sequence and induces fusion when expressed in mammalian cells.

The biological functions of the structural protein sigma C, from avian reovirus strain RAM-1, were investigated in this study. A putative fusion peptide in sigma C was recognized in the deduced amino acid sequence by homology with Pneumovirus fusion sequences, and it was thus postulated that this protein may be involved in the formation of syncytia in cells infected with RAM-1. The sigma C gene was cloned and expressed in mammalian (COS7) cells and the sigma C protein was found to induce syncytia. It was therefore concluded that this protein is indeed responsible for avian reovirus-induced cell fusion. It was also found that sigma C caused condensation of the nuclei within a syncytium, as observed in RAM-1-infected cells. On the basis that this represented condensation of the chromatin, the inhibition of cellular DNA synthesis by the virus and by the sigma C protein was measured. It was found that the virus caused a 50% reduction in cellular DNA synthesis, but the sigma C protein did not inhibit DNA synthesis. Therefore pyknosis of the nuclei and inhibition of cellular DNA synthesis by RAM-1 are likely to be separate events.

Molecular and serological analyses of two bovine rotaviruses (B-11 and B-60) causing calf scours in Australia.

Fecal specimens from 78 calves involved in outbreaks of calf diarrhea which occurred in three farms in Victoria, Australia, in 1988 were analyzed for rotaviruses. Thirty-eight samples were positive for group A virus antigen by enzyme-linked immunosorbent assay, and 20 of these contained viral double-stranded RNAs that could be detected by polyacrylamide gel electrophoresis. Two major electropherotypes could be observed, and a representative isolate of each electropherotype (isolates B-11 and B-60) was successfully adapted to grow in MA104 cells. Sequencing of the VP7 genes directly from RNA transcripts of fecal and cell culture-adapted viruses demonstrated that no base changes occurred in this gene upon adaptation to growth in MA104 cells. Sequencing also revealed that the VP7 protein of B-60 was closely related to G serotype 6 (G6) strains, whereas the B-11 sequence was significantly different from all previously published sequences except the recently reported VP7 sequences of bovine isolates 61A and B223, particularly across the antigenic regions A, B, and C. The other strains most closely related to B-11 by VP7 amino acid sequence analysis were G4 porcine strains BMI-1 and BEN-144 and G8 human strain 69M. Serotyping of B-11 and B-60 gave results that were in good agreement with the sequencing data. Hyperimmune typing sera clearly identified B-60 as a member of G6, whereas the B-11 strain reacted to moderate titers only with antisera to some G10 strains. Antiserum raised against B-11 neutralized some strains of G10 cross-reacted with porcine G4 type isolates BMI-1 and BEN-144 but not with other G4 strains or with rotaviruses of other mammalian G serotypes. Northern blot hybridization showed that B-11 was closely related to the recently reported bovine G10 strain B223, and they both possessed a similar segment 4 that was different from that of either UK bovine or NCDV rotavirus.

S100 protein-positive dendritic cells and the significance of their density in gastric precancerous lesions.

Quantitative analysis of dendritic cells (DC's) was carried out in tissue specimens of normal gastric mucosa (n = 15), gastric ulcer (n = 19), chronic atrophic gastritis (n = 28), and gastric carcinoma (n = 65) by ABC immunostaining with S100 protein antibody. Significant increases in DC number were observed in chronic atrophic gastritis with type III intestinal metaplasia and/or grade II, III dysplasia. The result suggests that DC's are potentially capable of presenting neoantigens associated with malignant transformation at the precancerous stage when malignant morphological changes have not yet taken place. Combined with routine diagnostic methods, the serial monitoring of DC density in gastric mucosa may be useful in the follow-up of premalignant lesions in the stomach and the diagnosis of early gastric carcinoma.

[Avidin-biotin-peroxidase complex enzyme-linked immunosorbent assay in the diagnosis of human multilocular echinococcosis].

The Avidin-Biotin-Peroxidase Complex enzyme-linked immunosorbent assay (ABC-ELISA) with antigen from gerbils infected with alveolar hydatid (GAH) was performed on the sera of 54 patients with multilocular echinococcosis, 107 patients with other diseases and 102 healthy adults. All the sera were diluted 1:200 and an S/N value greater than 2.2 was taken as positive. Both the sensitivity and specificity were 98.1%. The S/N value (mean +/- SD) of sera of the patients with multilocular echinococcosis, other parasitic diseases, tuberculosis, other diseases and healthy adults were: 5.9 +/- 3.0, 1.1 +/- 0.4, 1.4 +/- 0.8, 1.1 +/- 0.5 and 1.0 +/- 0.4. The geometric mean titre (GMT) of antibody measured by ABC-ELISA was 13.7 times that of ELISA. The quantity of serum used in ELISA was 8 times that of ABC-ELISA. ABC-ELISA might be particularly helpful to identify cases with low immune responsiveness. In the detection of alveolar hydatidosis and cystic disease with GAH antigens, the positivity was 98.1 and 67.1% with 87 and 25.6% having S/N greater than 5, respectively. It is suggested that in the diagnosis of hydatid diseases by ABC-ELISA, homologous antigen should be used. The temperature and the incubation time needed for the present assay are practical, for the total time requires only 55 minutes.